Nitric-oxide synthases compounds

Andrographolide, thus, has different mechanisms of anti-inflammatory activity. It can inhibit the activation of NF-kB, suppress inducible nitric oxide synthase (iNOS) expression, inhibit COX-2 expression in human fibroblast cells and also prevent oxygen radical production by human. The compound is also able to modulate T-cell activation both in vitro as well as in vivo, it is evident that it could prevent initial T-cell priming by interfering with DC maturation and antigen presentation capacity. Therefore, andrographolide may have utility as a therapeutic agent for the treatment of autoimmune diseases, such as multiple sclerosis. " ... 

Fukuto, J. M., Stuehr, D. J., Feldman, P. L., Bova, M. P., and Wong, P. (1993). Peracid oxidation of an N-hydroxyguanidine compound A chemical model for the oxidation of N-omega-hydroxyl-L-arginine by nitric oxide synthase. J. Med. Chem. 36, 2666-2670. 

Fig. (4). Vasodilatory mechanisms of flavonoids. RWPC red wine polyphenolic compounds NO nitric made NOSe nitric oxide synthase endothelial O2 superoxide anions OONO peroxynitrites PKC protein kinase Q AC adenylate cyclase GC guanylate cyclase PDE phosphodiesterase.

Ebselen and related compounds, among them carboxylated analog 59 (R = 4-C6H4COOH), have been reported to be inhibitors of constitutive endothelial nitric oxide synthase (ec NOS) [153, 258-260], Selenourea derivatives, among them 2-aminoselenazoline, are potent inhibitors of the iNOS [261],... 

Brenman JE, Chao DS, Gee SH, McGee AW, Craven SE, Santillano DR, Wu Z, et al. (1996) Interaction of nitric oxide synthase with the postsynaptic density protein PSD-95 and alpha 1-syntrophin mediated by PDZ domains. Cell 84 757-67 Broillet MC, Firestein S (1996) Direct activation of the olfactory cyclic nucleotide-gated channel through modification of sulfhydryl groups by NO compounds. Neuron 16 377-85... 

In summary, natural products have a few known general mechanisms of action. These include toxins, inhibitors of growth, surface-energy modifiers, nervous pathway interference (anesthetics, including nitric oxide synthase inhibitors and neurotransmitter blockers), inhibitors of attachment, inhibitors of metamorphosis, and repellants.46 55117118 It is likely that many compounds have multiple mechanisms of action. 

Other ESR studies include 2,2 -diamino-4,4 -bithiazole and 2,2 -bis(acetamido)-4,4 -bithiazole copper(ll) complexes <2000SRI1653>, patellamide A derivatives, and their copper(ii) compounds <2002CEJ1527>, endothelial nitric oxide synthase and its reaction with thiazole-containing ligand <1996JBC32563>. 

Inhibition of the enzyme has been shown with pentamidine and other aminoguanidine compounds -specifically aminoguanidine (pimagedine), some amiloride analogues, the alkaloid nazlinin and some derivatives, and metronidazole. Of these, aminoguanidine has mostly been used as a pharmacological tool in the past, but interpretation of findings is complicated by the recent demonstration that it is a potent nitric oxide synthase inhibitor. 

Dirsch V, Kiemer A, Wagner H, Vollmar A. Effect of allicin and ajoene, two compounds of garlic, on inducible nitric oxide synthase. Atherosclerosis 1998 139 333-339. 

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